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1دورية أكاديمية
المؤلفون: Marco Tagliamento, Marie Morfouace, Charalambos Loizides, Julio Oliveira, Laurent Greillier, Judith Raimbourg, Anne-Claire Toffart, Thierry Chatellier, Nicolas Cloarec, Ivana Sullivan, Birute Brasiuniene, Michael Duruisseaux, Kersti Oselin, Marie-Sophie Robert, Carolina Fernandes, Arnaud Poncin, Jean-Yves Blay, Benjamin Besse, Nicolas Girard
المصدر: npj Precision Oncology, Vol 8, Iss 1, Pp 1-5 (2024)
مصطلحات موضوعية: Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
الوصف: Abstract Arcagen (NCT02834884) is a European prospective study aiming at defining the molecular landscape of rare cancers for treatment guidance. We present data from the cohort of rare thoracic tumors. Patients with advanced pleural mesothelioma (PM) or thymic epithelial tumors (TET) underwent genomic profiling with large targeted assay [>300 genes, tumor mutational burden (TMB), microsatellite instability (MSI) status] on formalin-fixed paraffin-embedded (FFPE) or plasma samples. EORTC molecular tumor board (MTB) advised for biomarker-guided treatments. 102 patients recruited from 8 countries between July 2019 and May 2022 were evaluable: 56 with PM, 46 with TET (23 thymomas, 23 thymic carcinomas). Molecular profiling was performed on 70 FFPE samples (42 PM, 28 TET), and 32 cases on ctDNA (14 PM, 18 TET), within a median turnaround time of 8 days from sample reception. We detected relevant molecular alterations in 66 out of 102 patients (65%; 79% PM, 48% TET), 51 of 70 FFPE samples (73%; 90% PM, 46% TET), and 15 of 32 plasma samples (47%; 43% PM, 50% TET). The most frequently altered genes were CDKN2A/B, BAP1, MTAP in PM and TP53, CDKN2A/B, SETD2 in TET. The TMB was low (mean 3.2 Muts/MB), 2 PM had MSI-high status. MTB advised molecular-guided treatment options in 32 situations, for 17 PM and 15 TET patients (75% clinical trial option, 22% off-label drug or compassionate use, 3% early access program). Molecular testing and MTB discussion were feasible for patients with rare thoracic cancers and allowed the broadening of treatment options for 30% of the cases.
وصف الملف: electronic resource
العلاقة: https://doaj.org/toc/2397-768XTest
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2دورية أكاديمية
المؤلفون: Maximilian J. Hochmair, Mojca Unk, Jelena Spasic, Timur Cerić, Assia Konsoulova, Mircea Dediu, Krisztina Bogos, Alinta Hegmane, Kersti Oselin, Marko Stojiljkovic, Tina Roblek, Marko Jakopovic
المصدر: BMC Proceedings, Vol 18, Iss S3, Pp 1-7 (2024)
مصطلحات موضوعية: EGFR exon 20 insertion mutations, NSCLC treatment, Diagnostic challenges, Targeted therapies, Next-generation sequencing, Healthcare disparities in Central and Eastern Europe, Medicine, Science
الوصف: Abstract Lung cancer remains the leading cause of cancer-related deaths in Europe, with non-small cell lung cancer (NSCLC) accounting for approximately 85% of cases. NSCLC is a heterogeneous disease encompassing various oncogenic alterations. Among them, EGFR exon 20 insertion mutations, constituting 0.3–2.2% of NSCLC cases, rank as the third most common EGFR alteration after exon 19 deletions and the L858R point mutation in exon 21, also known as “typical” EGFR alterations. Recent advancements in understanding the molecular pathogenesis of NSCLC have led to significant breakthroughs in targeted therapies, revolutionizing treatment options for patients with specific genetic alterations. This article presents the outcomes of a Virtual Meeting conducted on the online platform (provided Within3©) from September 19 to October 30, 2022. The meeting focused on addressing the challenges in the diagnosis and treatment of NSCLC patients with EGFR exon 20 insertion mutations. The participants consisted of healthcare professionals from ten Central and Eastern European countries who shared their experiences and opinions on various aspects, including epidemiology, treatment options, and diagnostic approaches employed in their respective healthcare institutions. The discussions were facilitated through open-ended and multiple-choice questions. The primary objective of this article is to provide an overview of the identified challenges associated with the diagnosis and treatment of this heterogeneous disease, based on the assessments of the meeting participants. Among the major emerging challenges discussed, the reimbursement issues concerning next-generation sequencing (NGS), a recommended method in NSCLC molecular diagnosis, and the availability of approved targeted treatments to enhance patient outcomes were of paramount importance. Furthermore, fostering community awareness of lung cancer and promoting harmonized lung cancer care were identified as areas deserving greater attention. Notably, the rapidly evolving treatment landscape, particularly with NGS for NSCLC patients with genomic alterations like EGFR, ALK, RET, MET, NTRK, and ROS1, necessitates prioritizing the development of new drugs, even for the relatively smaller subgroup with exon 20 insertion mutations.
وصف الملف: electronic resource
العلاقة: https://doaj.org/toc/1753-6561Test
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3دورية أكاديمية
المؤلفون: Kersti Oselin, Heti Pisarev, Keit Ilau, Raul-Allan Kiivet
المصدر: BMC Cancer, Vol 21, Iss 1, Pp 1-10 (2021)
مصطلحات موضوعية: Advanced lung cancer, End-of-life care, High intensity care, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
الوصف: Abstract Background We aimed to study the mortality and intensity of health care in patients with advanced lung cancer who received systemic anti-cancer treatment (SACT) compared with patients who were not eligible for SACT (no-SACT). Methods A retrospective cohort of patients with lung cancer, who were treated at the North Estonia Medical Centre from 2015 to 2017, was linked to population-based health care data from the Estonian Health Insurance Fund. We calculated 14- and 30-day mortality after SACT and used a composite measure of intensity of care, comprised from the following: emergency department visit, admission to hospital, admission to intensive care unit, receipt of radiotherapy or systemic treatment. Results The median overall survival (OS) of patients who received at least one cycle of SACT (n = 489) was 9.1 months and in patients with no-SACT (n = 289) 1.3 months (hazard ratio [HR] = 4.23, 95% CI = 3.60–5.00). During the final 30 days of life, intensive EOL care was received by 69.9% of the SACT patients and 43.7% of the no-SACT patients. Intensive EOL care in the last 30 days of life is more probable among patients in the SACT group (odds ratio [OR] = 3.58, 95% CI = 2.54–5.04, p
وصف الملف: electronic resource
العلاقة: https://doaj.org/toc/1471-2407Test
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4دورية أكاديمية
المؤلفون: Anneli Uusküla, Mait Raag, Katrin Kurvits, Ott Laius, Maia Uusküla, Kersti Oselin
المصدر: Pharmacology Research & Perspectives, Vol 8, Iss 2, Pp n/a-n/a (2020)
مصطلحات موضوعية: Estonia, opioids, prescription drugs, Therapeutics. Pharmacology, RM1-950
الوصف: Abstract Our objective was to examine the trends and variation in opioid prescribing in Estonia from 2011 to 2017. This retrospective cross‐sectional study is based on a nationwide prescription medicines database. We stratified the analysis by treatment indication (cancer vs noncancer pain). Between 2011 and 2017, annual opioid prescribing rates increased by 67% (from 82.9 to 138.6 prescriptions per 1000 population). The annual number of prescriptions per patient did not change substantially (from 2.94 in 2011 to 2.87 in 2017), and was higher among cancer patients (5.07 vs 2.67 annual prescriptions per cancer and noncancer patients, respectively, in 2017). The use of the most potent opioids (morphine, fentanyl) was higher in noncancer than in cancer patients. The use of prescription opioids is low, and raises concern about the potential undertreatment of cancer pain, in parallel with misuse of opioids for either noncancer pain or diversion.
وصف الملف: electronic resource
العلاقة: https://doaj.org/toc/2052-1707Test
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5دورية أكاديمية
المؤلفون: Kersti Oselin, Heti Pisarev, Keit Ilau, Raul-Allan Kiivet
المصدر: Applied Sciences, Vol 11, Iss 19, p 9301 (2021)
مصطلحات موضوعية: resource use, health care, end of life care, advanced lung cancer, Technology, Engineering (General). Civil engineering (General), TA1-2040, Biology (General), QH301-705.5, Physics, QC1-999, Chemistry, QD1-999
الوصف: We aimed to study differences in the use of health care resources in relation to time before death in patients with advanced lung cancer who either received systemic anti-cancer treatment (SACT) or were ineligible for SACT. A retrospective cohort of lung cancer patients (N = 778) diagnosed with advanced disease at North Estonia Medical Centre from 2015–2017 was linked to population-based health care data. We calculated a composite measure of cumulative resource use, comprised from the following: outpatient care, emergency department (ED) visit, inpatient care, admission to intensive care unit, nursing care and prescriptions. Costs were highest in patients who received SACT in the last month before death and decreased in parallel with the time elapsed from the last SACT. Only 20% of SACT patients received nursing care in the final month of life. The no-SACT patients had less time covered by health care services per month, and large differences were seen in the type of service received by the study groups. The largest contributor of health care costs at end of life was acute inpatient care, including approximately 10% of patients who died on the same day as or day following the emergency department visit. These results demonstrate the low nursing care and hospice utilization rates in Estonia.
وصف الملف: electronic resource
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6دورية أكاديمية
المؤلفون: Kersti Oselin (10307478), Heti Pisarev (10307481), Keit Ilau (10307484), Raul-Allan Kiivet (10307487)
مصطلحات موضوعية: Medicine, Cell Biology, Biotechnology, Cancer, Science Policy, Computational Biology, Biological Sciences not elsewhere classified, Advanced lung cancer, End-of-life care, High intensity care
الوصف: Additional file 1: Supplemental Table 1. Use of systemic anti-cancer treatment in patients with advanced lung cancer. Supplemental Table 2. Myelotoxicity and infectious complications in patients with and without 14- and 30-day mortality after last cycle of systemic anti-cancer treatment.
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المؤلفون: Mary O’Brien, Luis Paz-Ares, Sandrine Marreaud, Urania Dafni, Kersti Oselin, Libor Havel, Emilio Esteban, Dolores Isla, Alex Martinez-Marti, Martin Faehling, Masahiro Tsuboi, Jong-Seok Lee, Kazuhiko Nakagawa, Jing Yang, Ayman Samkari, Steven M Keller, Murielle Mauer, Nitish Jha, Rolf Stahel, Benjamin Besse, Solange Peters
المصدر: The Lancet Oncology. 23:1274-1286
مصطلحات موضوعية: Myocarditis, Lung Neoplasms, Oncology, Carcinoma, Non-Small-Cell Lung, Antineoplastic Combined Chemotherapy Protocols, Hypertension, Humans, Antibodies, Monoclonal, Humanized, B7-H1 Antigen
الوصف: Pembrolizumab is a standard-of-care for advanced non-small-cell lung cancer (NSCLC). We assessed pembrolizumab as adjuvant therapy for completely resected stage IB-IIIA NSCLC.In this randomised, triple-blind, phase 3 trial (PEARLS/KEYNOTE-091), patients were recruited from 196 medical centres in 29 countries. Eligible patients were aged 18 years or older, with completely resected, pathologically confirmed stage IB (tumours of ≥4 cm in diameter), II, or IIIA NSCLC per the American Joint Committee on Cancer staging system (7th edition) of any histology or PD-L1 expression level, and an Eastern Cooperative Oncology Group performance status of 0 or 1; adjuvant chemotherapy was to be considered for stage IB disease and was strongly recommended for stage II and IIIA disease, according to national and local guidelines. Using a central interactive voice-response system, eligible participants were randomly assigned (1:1), using a minimisation technique and stratified by disease stage, previous adjuvant chemotherapy, PD-L1 expression, and geographical region, to pembrolizumab 200 mg or placebo, both administered intravenously every 3 weeks for up to 18 cycles. Participants, investigators, and analysts were masked to treatment assignment. Dual primary endpoints were disease-free survival in the overall population and in the population with PD-L1 tumour proportion score (TPS) of 50% or greater. Efficacy was assessed in the intention-to-treat (ITT) population (ie, all participants randomly assigned to a treatment group). Safety was assessed in all participants randomly assigned to treatment who received at least one dose of study treatment. Here we report results of the second interim analysis, prespecified to occur when approximately 118 disease-free survival events had occurred in the PD-L1 TPS of 50% or greater population. This study is registered with ClinicalTrials.gov, NCT02504372, and is active but not recruiting.Between Jan 20, 2016, and May 6, 2020, 1177 (60%) of 1955 screened participants were randomly assigned to pembrolizumab (n=590, including n=168 with PD-L1 TPS of ≥50%) or placebo (n=587; including n=165 with PD-L1 TPS of ≥50%) and included in the ITT population. Median follow-up as of data cutoff (Sept 20, 2021) for this interim analysis was 35·6 months (IQR 27·1-45·5). In the overall population, median disease-free survival was 53·6 months (95% CI 39·2 to not reached) in the pembrolizumab group versus 42·0 months (31·3 to not reached) in the placebo group (HR 0·76 [95% CI 0·63-0·91], p=0·0014). In the PD-L1 TPS of 50% or greater population, median disease-free survival was not reached in either the pembrolizumab group (95% CI 44·3 to not reached) or the placebo group (95% CI 35·8 to not reached; HR 0·82 [95% CI 0·57-1·18]; p=0·14). Grade 3 or worse adverse events occurred in 198 (34%) of 580 participants who received pembrolizumab and 150 (26%) of 581 participants who received placebo. Grade 3 or worse events that occurred in at least ten participants in either treatment group were hypertension (35 [6%]) and pneumonia (12 [2%]) with pembrolizumab and hypertension (32 [6%]) with placebo. Serious adverse events occurred in 142 (24%) participants in the pembrolizumab group and 90 (15%) in the placebo group; serious adverse events that occurred in more than 1% of participants were pneumonia (13 [2%]), pneumonitis (12 [2%]), and diarrhoea (seven [1%]) with pembrolizumab and pneumonia (nine [2%]) with placebo. Treatment-related adverse events led to death in four (1%) participants treated with pembrolizumab (one due to both cardiogenic shock and myocarditis, one due to both septic shock and myocarditis, one due to pneumonia, and one due to sudden death) and in no participants treated with placebo.Pembrolizumab significantly improved disease-free survival compared with placebo and was not associated with new safety signals in completely resected, PD-L1-unselected, stage IB-IIIA NSCLC. Pembrolizumab is potentially a new treatment option for stage IB-IIIA NSCLC after complete resection and, when recommended, adjuvant chemotherapy, regardless of PD-L1 expression.Merck Sharpamp; Dohme, a subsidiary of Merckamp; Co.
الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::546d56085895273ebf924ed87a7e4b0bTest
https://doi.org/10.1016/s1470-2045Test(22)00518-6 -
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المؤلفون: Mary E.R. O'Brien, Luis Paz-Ares, Nitish Jha, Urania Dafni, Kersti Oselin, Libor Havel, Emilio Esteban, Dolores Isla, Alex Martinez-Marti, Martin Faehling, Masahiro Tsuboi, Jong-Seok Lee, Kazuhiko Nakagawa, Jing Yang, Steven M. Keller, Murielle Mauer, Sandrine Marreaud, Rolf A. Stahel, Benjamin Besse, Solange Peters
المصدر: Journal of Clinical Oncology. 40:8512-8512
مصطلحات موضوعية: Cancer Research, Oncology
الوصف: 8512 Background: At the second interim analysis (IA2) of the triple-blind, phase 3 PEARLS/KEYNOTE-091 study (NCT02504372), pembrolizumab significantly improved DFS compared with placebo in patients (pts) with completely resected stage IB (T ≥4 cm) to IIIA NSCLC per AJCC v7, regardless of PD-L1 expression (N = 1177, HR 0.76, 95% CI 0.63-0.91, P = 0.0014). We present DFS in subgroups related to surgery, disease burden, and adjuvant chemotherapy use. Methods: Pts had pathologically confirmed, completely resected stage IB (T ≥4 cm) to IIIA NSCLC of any PD-L1 expression and ECOG PS 0-1. Systematic complete or lobe-specific mediastinal lymph node dissection was recommended; minimally, the subcarinal and 1 lobe-specific lymph node must have been examined. Adjuvant chemotherapy of ≤4 cycles was given as indicated by local guidelines. Eligible pts were randomized 1:1 to pembrolizumab 200 mg or placebo Q3W for 18 doses (̃1 y). Treatment effects on DFS were assessed in prespecified subgroups of with and without adjuvant chemotherapy and in exploratory subgroups defined by surgery type, pN stage, tumor size, no. of adjuvant chemotherapy cycles, and adjuvant regimen; only subgroups of > 50 pts were analyzed. Data cutoff for IA2 was September 20, 2021 (median time from randomization to cutoff, 35.6 mo). Results: By surgery type, the HR (95% CI) for DFS was 0.78 (0.64-0.96) for lobectomy (n = 925), 0.85 (0.43-1.69) for bilobectomy (n = 92), and 0.71 (0.40-1.24) for pneumonectomy (n = 127). For subgroups based on nodal status, HR (95% CI) for DFS was 0.63 (0.46-0.86) for pN0 (n = 490), 0.77 (0.57-1.03) for pN1 (n = 456), and 1.00 (0.71-1.41) for pN2 (n = 231). By tumor size, and irrespective of nodal status, the HR (95% CI) for DFS was 0.91 (0.69-1.20) for size ≤4 cm (n = 491) and 0.70 (0.55-0.89) for size > 4 cm (n = 685). The HR (95% CI) for DFS was 0.73 (0.60-0.89) in pts who received adjuvant chemotherapy (n = 1010) and 1.25 (0.76-2.05) in those who did not (n = 167). Among pts who received adjuvant chemotherapy, HR (95% CI) for DFS by number of cycles was 0.59 (0.28-1.26) for 1-2 (n = 67) and 0.74 (0.61-0.91) for 3-4 (n = 943); by regimen, it was 0.74 (0.55-0.98) for cisplatin + vinorelbine (n = 491), 0.51 (0.31-0.83) for carboplatin + vinorelbine (n = 151), 1.21 (0.73-1.98) for carboplatin + paclitaxel (n = 135), 0.65 (0.30-1.40) for cisplatin + gemcitabine (n = 57), and 0.68 (0.41-1.14) for other regimen (n = 176). Conclusions: Pembrolizumab generally improved DFS versus placebo regardless of type of surgery, lymph node involvement, tumor size, and type and extent of adjuvant chemotherapy in pts with completely resected stage IB (T ≥4 cm) to IIIA NSCLC. These data support the benefit of pembrolizumab as adjuvant therapy for early-stage NSCLC following complete resection and, if indicated, adjuvant chemotherapy. Clinical trial information: NCT02504372.
الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_________::0bf1c25d1215a9e26c7e1a55aa5f7a8fTest
https://doi.org/10.1200/jco.2022.40.16_suppl.8512Test -
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المؤلفون: Tuuli Metsvaht, Irja Lutsar, Helgi Padari, Tõnis Tasa, Karin Kipper, Koit Herodes, Hiie Soeorg, Kersti Oselin, Maarja Hallik, Mari-Liis Ilmoja
المصدر: The Pediatric infectious disease journal. 40(5)
مصطلحات موضوعية: Microbiology (medical), medicine.medical_specialty, medicine.drug_class, Antibiotics, Population, Gestational Age, Microbial Sensitivity Tests, Gastroenterology, Group B, 03 medical and health sciences, 0302 clinical medicine, Pharmacokinetics, 030225 pediatrics, Internal medicine, Ampicillin, medicine, Humans, 030212 general & internal medicine, Prospective Studies, Prospective cohort study, education, Volume of distribution, education.field_of_study, Models, Statistical, business.industry, Infant, Newborn, Gestational age, Anti-Bacterial Agents, Infectious Diseases, Pediatrics, Perinatology and Child Health, Epidemiological Models, Neonatal Sepsis, business, medicine.drug
الوصف: Background and aims Ampicillin is 1 of the most commonly used antibiotics for treatment of early onset sepsis, but its pharmacokinetics (PK) is poorly characterized. We aimed to define the dose of ampicillin for late preterm and term neonates by evaluating its PK in serum, cerebrospinal (CSF), and epithelial lining fluid. Methods A prospective study included neonates receiving ampicillin for suspected or proven early onset sepsis and pneumonia. PK samples were collected at steady state, at predose and 5 minutes, 1 hour, 3 hours, 8 hours, and 12 hours after ampicillin 3-minute infusion. Ampicillin concentrations were measured by ultra-high-performance liquid chromatography. Noncompartmental anaysis (NCA) and population pharmacokinetic (pop-PK) modeling were performed and probability of therapeutic target attainment was simulated. Results In 14 neonates (GA of 32-42 wks; mean BW 2873 g), PK parameters (mean ± SD) in NCA were the following: half-life 7.21 ± 7.97 hours; volume of distribution (Vd) 1.07 ± 0.51 L; clearance (CL) 0.20 ± 0.13 L/h; 24-hour area under the concentration-time curve 348.92 ± 114.86 mg*h/L. In pop-PK analysis, a 2-compartmental model described the data most adequately with the final parameter estimates of CL 15.15 (CV 40.47%) L/h/70kg; central Vd 24.87 (CV 37.91%) L/70kg; intercompartmental CL 0.39 (CV 868.56) L/h and peripheral Vd 1.039 (CV 69.32%) L. Peutic target attainment simulations demonstrated that a dosage of 50 mg/kg q 12 hours attained 100% fT > MIC 0.25 mg/L, group B streptococcal breakpoint. Conclusions We recommend ampicillin dosage 50 mg/kg q 12 hours for neonates with gestational age ≥32 weeks during the first week of life.
الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::e2989691861fc3f75efbd6f0996afb3fTest
https://pubmed.ncbi.nlm.nih.gov/33591074Test -
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المؤلفون: Kersti Oselin, Heti Pisarev, Keit Ilau, Raul-Allan Kiivet
الوصف: Background: We aimed to study the mortality and intensity of health care in patients with advanced lung cancer assigned to systemic anti-cancer treatment (SACT) compared with patients who were not eligible for SACT (no-SACT). Methods: A retrospective cohort of lung cancer patients, who were treated at the North Estonia Medical Centre from 2015–2017, was linked to population-based health care data from the Estonian Health Insurance Fund. We calculated 14- and 30-day mortality after SACT and used a composite measure of intensity of care, comprised from the following: emergency department visit, admission to hospital, admission to intensive care unit, receipt of radiotherapy or systemic treatment. Results: The median overall survival (OS) of patients who received at least one cycle of SACT (n = 489) was 9.1 months and in patients with no-SACT (n = 289) 1.3 months (hazard ratio [HR]=4.23, 95% CI=3.60-5.00). In the SACT group 6.7% and 14.7% of patients died within 14 days and 30 days after the last cycle, respectively. During the final 30 days of life, intensive EOL care was received by 69.9% of the SACT patients and 43.7% of the no-SACT patients (p < 0.001). Among SACT patients, sepsis, bacterial infection and/or neutropenia had a significant adverse effect on survival (HR=1.7, 95% CI=1.3-2.21, p < 0.001), whereas the use of the granulocyte colony stimulating growth factor reduced the risk of death (HR= 0.71, 95% CI=0.55-0.93, p = 0.013). Conclusions: Significant proportions of patients with advanced lung cancer continue to receive intensive care near death. Our results highlight that neutropenia and infectious complications are still the primary cause of early SACT-related death.
الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_________::a804a92f64fc33faf636acad5588062cTest
https://doi.org/10.21203/rs.3.rs-19211/v1Test
النص الكامل